Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During Kidney Transplantation

NCT04005469 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 974570-5
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this study are to test the preliminary safety and efficacy of a two-day peri-operative course of treprostinil in reducing ischemia-reperfusion injury in adult patients receiving a deceased donor kidney transplantation. Treprostinil, a prostacyclin analog, is expected to facilitate the restoration of blood supply to the revascularized kidney graft via its vasodilatory actions, well characterized protective effects, and longer elimination half-life. These properties and actions of treprostinil make it a strong drug candidate to reduce kidney graft dysfunction during kidney transplantation. An anticipated 20 participants undergoing deceased donor kidney transplant will be hospitalized and intensively monitored during an entire two-day Treatment Phase. An IV infusion using a dedicated central venous line will be used to administer treprostinil commencing approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of the transplant surgery. The primary endpoints include the safety and efficacy of treprostinil, with secondary endpoints including the evaluation of both biochemical and clinical endpoints post-transplantation.

Conditions

Ischemia Reperfusion Injury; Delayed Graft Function

Keywords

Ischemia-reperfusion injury; kidney transplantation; prostacyclin; treprostinil; delayed graft function

Outcome Measures

Primary Outcomes (1)

• Serum creatinine (SCr)

  Primary efficacy assessment will include the cGFR using SCr during the first seven days post transplantation.

  Day 1-7

Secondary Outcomes (4)

• INR

  Day 7

• Urine output

  Day 7

• Primary graft non-function; kidney failure

  Day 30

• Delayed graft function

  Day 30

Study Arms (1)

Trepostinil

EXPERIMENTAL

Treprostinil (Remodulin) will be administered IV by a standard 3 + 3 dose-escalation approach. This dosing model will be followed until a target dose of 15 mg/kg/min is achieved or if it is medically determined that side effects prevent dose escalation. IV infusion will commence approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of surgery, unless hemodynamic changes or tolerability require discontinuation of treprostinil.

Drug: Treprostinil

Interventions

Treprostinil DRUG

Treprostinil (Remodulin) will be administered IV by a standard 3 + 3 dose-escalation approach. This dosing model will be followed until a target dose of 15 mg/kg/min is achieved or if it is medically determined that side effects prevent dose escalation. IV infusion will commence approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of surgery, unless hemodynamic changes or tolerability require discontinuation of treprostinil.

Also known as: Remodulin®

Trepostinil

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients who will receive a deceased donor kidney aged 18 to 65 (inclusive) and are currently on the active transplant list at RIH.
• Documentation of a diabetes diagnosis as evidenced by one or more clinical features consistent will be noted for all patients.
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

You may not qualify if:

• Under the age of 18 years
• Difficult venous access
• BMI \> 40 kg/m2
• Patients with severe clinical gastroparesis as determined by repeated vomiting
• Prior GI surgery except for cholecystectomy, appendectomy, or Nissen fundoplication
• Known or history of inflammatory bowel disease or bezoars
• History of diverticulitis, diverticular stricture, and other intestinal strictures
• Be receiving any investigational drug other than treprostinil or participating in any other investigational study
• Be receiving any prostanoid therapy to treat portopulmonary hypertension
• Have any known hypersensitivity to prostaglandins, prostacyclin or treprostinil
• Have had a failed kidney transplant within the previous 180 days
• Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results
• Those with significant cardiovascular disease including treatment with inotropes
• If female, be pregnant or nursing (confirmed by urine test)
• Presence of a condition or abnormality that in the opinion of the Investigators that would compromise the safety of the patient or the quality of the data

Sponsors & Collaborators

• Rhode Island Hospital: lead
• University of Rhode Island: collaborator
• United Therapeutics: collaborator

Study Sites (1)

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

MeSH Terms

Conditions

Reperfusion Injury; Delayed Graft Function

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

George Bayliss, MD

CONTACT

401-444-8562; gbayliss@Lifespan.org

Nisanne Ghonem, PharmD, PhD

CONTACT

401-874-4805; nghonem@uri.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Treprostinil will be administered intravenously by a standard 3 + 3 dose-escalation approach. The first three patients will receive a starting rate of 1.25 ng/kg/min and if all three patients safely tolerate the first dose, the next three patients will receive a dose of 2.5 ng/kg/min. If any patients experience side effects, additional patients will receive the previous lower dose. This dosing model will be followed until a target dose of 15 mg/kg/min is achieved or if it is medically determined that side effects prevent dose escalation.

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: July 2, 2019
• Study Start: November 13, 2020
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)